A new advance in cardiovascular medicine is launched today

Procoralan’s combination of efficacy and tolerability through selective heart rate reduction is a step forward in angina management

The new alternative for stable angina patients who have a contraindication or intolerance to beta-blockers, has been launched in the UK today by Servier Laboratories. Procoralan^▼ (ivabradine) has now gained full European approval and is the first of a new type of anti-anginal treatments – a selective sinus node I_f inhibitor.¹

Professor Kim Fox, Royal Brompton Hospital , London , is confident that the launch of Procoralan is a significant step forward in the treatment of stable angina. “Procoralan offers an excellent new option for the many patients who are unable to take beta-blockers due to intolerance or contraindications, without compromising on efficacy”, says Professor Fox. “This novel agent is effective and very well tolerated and is one of the most important advances in cardiovascular treatment over the last two decades.”

Procoralan is as effective as the beta-blocker atenolol and has been shown to deliver significant anti-anginal and anti-ischaemic benefits through its unique mode of action; selective heart rate reduction through inhibition of the sinus node I_f channels.¹

Angina affects around 2 million people in the UK² and currently a significant number of those have limited treatment options due to contraindications or tolerability problems with beta-blockers. Around a quarter of those with angina cannot tolerate beta-blockers and a further 15% of patients are contraindicated.³

Procoralan will provide a new alternative for such patients as it is not associated with the same common side effects seen with beta-blockers such as fatigue, low libido and cold extremities, which can have a significant impact on quality of life and compliance with treatment.^1,4

Dr Ahmet Fuat, a GP specialist in cardiology and PCCS deputy chairman, has welcomed the launch of Procoralan as a significant advance in the treatment of stable angina. “Finding a suitable alternative to beta-blockers for those who can’t take them has been a difficult problem,” said Dr Fuat. “Procoralan represents a new option for these patients and fills a long standing unmet need. The fact that it offers the efficacy of a beta-blocker without the same side-effects makes this a very important advance in angina management.”

Highlighting the unmet need in terms of new treatments for angina which has, until now, existed, a recent survey of 75 UK cardiologists showed that:

·         around 70% felt side effects were the main drawback of current treatments⁵

·         around 85% of cardiologists stated they would be likely to use a new treatment for angina that had a selective mode of action and reduced the risk of side effects associated with current angina treatments⁵

·         88% agreed or strongly agreed that reduction of heart rate is an important therapeutic goal in angina management⁵

Healthcare professionals are advised that treatment with Procoralan is likely to be initiated in secondary care settings and continued in primary care. For further information GPs are advised to contact their local cardiologist or visit www.procoralan.co.uk.

 
About Procoralan
Procoralan is the first selective sinus node If inhibitor and selectively reduces heart rate while maintaining cardiac contractility and atrioventricular conduction. It is indicated for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who have contraindication to, or intolerance for, beta-blockers such as those with asthma, COPD, PVD or diabetes. The starting dose is 5mg b.i.d. with titration up to 7.5mg as necessary.4,6
  
Procoralan is not associated with the classic side effects often seen with beta-blockers such as fatigue, loss of libido and cold extremities, and is generally very well-tolerated.  Visual effects, (described as ¡°phosphenes¡± in the Procoralan summary of product characteristics) presenting as mild, transient light spots have been observed in some patients. These resolved in 77.5% of patients during treatment and in all patients after treatment discontinuation and were due to the pharmacological activity of Procoralan. Less than 1% of patients withdrew from trials due to these visual effects, there was no evidence of toxic effect on the eye and patients can still drive when taking Procoralan.4
  
Procoralan is currently part of the largest clinical programme ever carried out to evaluate anti-ischaemic and anti-anginal efficacy with exercise tests. The ongoing clinical development programme conducted by Servier
involves more than 15,000 patients and investigates its efficacy in angina, post myocardial infarction, and heart failure.7

I_f channels – key facts

What are the I_f channels?

The  I_f channels are part of the electrical currents surrounding the sino-atrial node in the heart, a small group of specialised cells which form the heart’s natural pacemaker. Electrical impulses begin at the sino-atrial node and spread through the heart causing it to contract so that blood is pumped to the lungs and the rest of the body.¹

·         The I_f channels were discovered in Oxford in 1979 by Professor Dario DiFrancesco.

Where are the I_f channels expressed?

·         The I_f channels are mainly present in the membrane of the pacemaker cells in the sinus node. However, I_f channels are also expressed in other cardiac regions, such as the atrioventricular node and the ventricular conduction pathways but are inactive in these areas.^2,3

What is the role of the I_f channels?

·         The I_f channels contribute to both the creation and automatic altering of heart rate by controlling the slope of diastolic depolarisation and is the mechanism by which it controls heart rate.⁴

·         By affecting the I_f channels, the heart rate can be altered. Heart rate is becoming increasingly recognised as having important prognostic implications and a means of lowering heart rate without affecting other functions could have a significant impact on clinical practice.⁵

Why are the I_f channels important in cardiovascular medicine?

·         Inhibiting the I_f channels causes heart rate reduction which has important therapeutic implications. Recent trials have shown that the I_f channels can be selectively inhibited leading to a reduction in heart rate.⁴

·         Increased heart rate is an independent risk marker for cardiovascular morbidity and mortality. Reducing heart rate is considered to be helpful in preventing angina and is thought to be linked to wider cardiovascular benefits such as delaying the progression of coronary atherosclerosis.⁵

·         Because the sino-atrial node has a number of other currents which continue to function if the I_f channel is inhibited, negative effects such as bradycardia and heart block can be avoided.

New developments targeting the I_f channels?

·         Procoralan (ivabradine) is the first selective sinus node I_f inhibitor which selectively reduces heart rate by specific action on the sino-atrial node.⁶ Unlike some other treatments which also reduce heart rate, Procoralan does not influence myocardial contractility or blood pressure, and it preserves atrioventricular conduction and vascular repolarisation.⁶

See also ANGINA - NEW ENTITY

(1/2/06)